SILVER-STAINED NUCLEOLAR ORGANIZER PROTEINS IN UROTHELIAL BLADDER LESIONS - A MORPHOMETRIC STUDY

The diagnostic value of image analysis of silver-stained nucleolar organizer regions (AgNORs) has been investigated in 170 urothelial bladder lesions obtained by transurethral biopsies in the same number of patients. According to the WHO classification 25 specimens showed a flat non-invasive growth pattern with simple hyperplasia or mild dysplasia (H/D1 = 10), as well as moderate (D2 = 10) to servere atypia (Cis = 5). 135 samples were of papillary and/or infiltrating type including polypoid cystitis (pC = 5), true papillomas (G0 = 7), and carcinomas of different malignancy grade (G1 = 30, G2 = 55, G3 = 38). 10 biopsies served as normal controls. Benign non-neoplastic urothelium (controls, H/D1, pC) exhibited few but large AgNORs (mean number [MNN] = 3.3 +/- 0.5, mean area [MNA] = 0.29 +/- 0.08-mu-m2), whereas carcinomatous lesions (Cis, G1-G3) showed numerous small silver-stained dots within their nuclei (MNN = 6.9 +/- 1.1; MNA = 0.12 +/- 0.04-mu-m2). Both parameters, MNN and MNA, were inversely correlated (r = -0.69, p < 0.001); their quotient (NQ = MNN/MNA) revealed a clear cut difference in the AgNOR content of benign (control, H/D1: NQ = 12.8 +/- 2.5) and moderate to severe atypical flat urothelial lesions (D2, Cis: NQ = 44.2 +/- 12.8, p < 0.001). This parameter also discriminated between G1 (NQ = 40.7 +/- 17.3), G2 (NQ = 57.5 +/- 18.8), and G3 carcinomas (NQ = 79.0 +/- 21.8, p < 0.01). It is concluded that image analysis of AgNORs contributes to a reliable discrimination of higher degrees of dysplasia in flat and malignancy grading in papillary urothelial bladder lesions.